Medical Center for Human Reproduction, Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100069, PR China.
Nanjing Drum Tower Hospital Center of Molecular Diagnostic and Therapy, Institute for Brain Sciences, Jiangsu Engineering Research Center for MicroRNA Biology and Biotechnology, NJU Advanced Institute of Life Sciences (NAILS), School of Life Sciences, Nanjing University, Nanjing, 210046, China.
Biochem Biophys Res Commun. 2021 Mar 19;545:195-202. doi: 10.1016/j.bbrc.2021.01.079. Epub 2021 Feb 8.
Epilepsy is accompanied by abnormal neurotransmission, and microRNAs, as versatile players in the modulation of gene expression, are important in epilepsy pathology. Here, we found that miR-128 expression was elevated in the acute seizure phase and decreased during the recurrent seizure phase after status epilepticus in mice. Both SNAP-25 and SYT1 are regulated by miR-128 in vitro and in vivo. Overexpressing miR-128 in cultured neurons decreased neurotransmitter released by suppressing SNAP-25 and SYT1 expression. Anti-miR-128 injection before kainic acid (KA) injection increased the sensitivity of mice to KA-induced seizures, while overexpressing miR-128 at the latent and recurrent phases had a neuroprotective effect in KA-induced seizures. Our study shows for the first time that miR-128, a key regulator of neurotransmission, plays an important role in epilepsy pathology and that miR-128 might be a potential candidate molecular target for epilepsy therapy.
癫痫伴有异常的神经递质传递，而 microRNAs 作为基因表达调控的多功能因子，在癫痫病理中具有重要作用。在这里，我们发现 miR-128 在小鼠癫痫持续状态后的急性发作阶段表达升高，而在复发性发作阶段则降低。SNAP-25 和 SYT1 均受 miR-128 的体外和体内调控。在培养神经元中过表达 miR-128 通过抑制 SNAP-25 和 SYT1 的表达减少神经递质的释放。在 KA 注射前注射抗 miR-128 增加了小鼠对 KA 诱导的癫痫发作的敏感性，而在潜伏和复发性阶段过表达 miR-128 在 KA 诱导的癫痫发作中具有神经保护作用。我们的研究首次表明，作为神经递质关键调节因子的 miR-128 在癫痫病理中发挥重要作用，miR-128 可能是癫痫治疗的潜在候选分子靶点。
